To more fully describe trends in difficult to treat resistance, we used large de-deidentifed database from 173 hospitals with linked microbiologic, clinical, and demographic information (PremierTM) to describe DTR encounter characteristics, 5-year trends in prevalence and graded relationship with risk of mortality. We included unique inpatient encounters between 2009-13 with 1 GN bloodstream infections (BSI). DTR was defined by laboratory interpretations, as reported to providers. Our main outcome measures incuded: (1) Annual percent change (APC) in DTR and (2) Odds ratio (OR) of in-hospital mortality by DTR strata (non-DTR, DTR-2, DTR-1 and full DTR for >2, 2, 1 and 0 active high-efficacy, low-toxicity HELT antibiotics, respectively) using multivariable logistic regression. Of 43,164 unique patients with GNBSIs between 2009-2013, 2689 (6%) cases at 143 (83%) hospitals displayed some level of DTR with 434 (1%) at 90 (52%) hospitals meeting criteria for full DTR. DTR was associated with hospital-onset, older age, ICU admission and longer hospital stays. At 42 hospitals with continuous reporting, DTR decreased significantly among Klebsiella spp. (APC=-11%; p=0.03), Enterobacter spp. (APC=-16%; p=0.02) and P. aeruginosa (APC=-7%; p<0.001) and demonstrated a non-significant trend among A. baumannii (APC=-5%; p=0.21). Observed decreases likely underestimate true decreases in resistance due to the downward adjustment of breakpoints during the study. In contrast, E. coli GNBSI encounters demonstrated an increase in DTR (APC=12%; p<0.001), but this effect may be overestimated due to the same changes in breakpoints. On multivariable analysis, GNBSI mortality increased linearly with rising DTR strata; 20% for patients with DTR-2 (OR=1.2, 95% CI=1.0-1.4; p=0.02), 40% for DTR-1 (OR=1.4, 95% CI=1.2-1.7; p<0.0001) and 60% for full DTR (OR=1.6, 95% CI=1.2-2.0; p<0.0005) compared to non-DTR GNBSIs. After adjusting for patient, organism and hospital-level characteristics, DTR status remained an independent predictor of death (AUROC= 0.82). In U.S. hospitals over 5 years, DTR among GNBSIs remained infrequent and unexpectedly decreased over time; providers lacked safe and highly effective antibiotics for only 1% of GNBSIs. DTR was an independent predictor of mortality that might be useful to benchmark the impact of infection control measures on the burden of antimicrobial resistance.